There is a need for improved antiparasitic agents for use with animals, and in particular there is a need for improved insecticides and acaricides. Furthermore there is a need for improved topical and oral products with convenient administration and which contain one or more of such antiparasitic agents which can be used to effectively treat ectoparasites, such as insects (e.g., fleas, lice, and flies), acarids (e.g., mites and ticks), and crustaceans (e.g., copepods-sea lice). Such products would be particularly useful for the treatment of companion animals, such as cats, dogs, llamas, and horses; livestock, such as cattle, bison, swine, sheep, and goats; birds, such as chickens, ducks, and geese; and fish.
The compounds currently available for insecticidal and acaricidal treatment of companion animals and livestock do not always demonstrate good activity, good speed of action, or a long duration of action. Most treatments contain hazardous chemicals that can have serious consequences, including lethality from accidental ingestion. Persons applying these agents are generally advised to limit personal exposure. Pet collars and tags have been utilized to overcome some problems, but these are susceptible to chewing, ingestion, and subsequent toxicological affects to the animal. Thus, current treatments achieve varying degrees of success which depend partly on toxicity, method of administration, and efficacy. Currently, some agents are actually becoming ineffective due to parasitic resistance.
Naphthalene isoxazolines have been disclosed in the art as having insecticidal and acaricidal activity, for example WO2007/079162, WO2008/154528, and WO2009/002809. These publications disclose naphthyl carboxamides and other amide derivatives. Isoxazoline phenyl-oxime derivatives have been disclosed in publication WO2005/085216. A US equivalent patent, U.S. Pat. No. 7,662,972, discloses examples of these phenyl oximes. These phenyl oximes were shown to have an insecticidal rate of 80% or more at concentrations of 100 ppm and 500 ppm. WO2009/025983 provides methods of preparing isoxazoline substituted 1-naphthalenyl compounds, specifically with bromine, carboxylate, and carboxamide substituents. Despite the availability of effective, broad spectrum antiparasitic and insecticidal agents, there remains a need for a safer, convenient, and environmentally friendly product that will overcome the ever-present threat of resistance development.
These citations do not exemplify nor disclose any isoxazoline naphthyl oximes derivatives, nor does the prior art indicate that such compounds would be useful against a spectrum of parasitic species relevant to companion animals, livestock, birds, or fish, or against the range of parasitic morphological lifecycle stages.
The present invention overcomes one or more of the various disadvantages of, or improves upon, the properties of existing compounds. In particular the present invention provides new isoxazoline substituted naphthyl oximes which demonstrate such properties.